Throughout history eating fish has been associated with good health, fertility, and helpful in alleviating many illnesses. In the late 1700s a clinic in Manchester, England discovered that cod liver oil miraculously “healed” chronic pain from arthritis and the news spread quickly across Europe and gave rise to the popularity of the oil.
In the 1970s, two Danish researchers theorized that the cardiac benefits of eating fish were linked to a fatty acid group called the Omega 3s, which make up approximately 10 to 30 wt % of extracted fish oil while the remainder of the oil is comprised of saturated, mono unsaturated, and other poly unsaturated parts. Among the Omega 3 fatty acids, two fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) were particularly prevalent and garnered great scientific and popular notoriety. However, researchers ignored the fact that, for example, cod liver oil not only contains EPA and DHA but also more than 10 other types of Omega 3 fatty acids. Moreover, many fish oils include endogenous vitamins such as Vitamins A, D, E, Cofactors such as CoQ10, and melatonin, but ratios and concentrations of these vitamins, cofactors, and melatonin vary dramatically across fish species.
Due to the positive effects associated with fish oils, many clinical trials have been conducted with various fish oils, DHA formulations, EPA formulations, and/or DHA/EPA formulations, but these trials generally ignore the fact that concentrations of fatty acids, vitamins, cofactors, and melatonin vary dramatically across fish species. Moreover, these trials further ignore how this variation affects a subject's epigenetic response (e.g., gene expression) when administered with these formulations. The ultimate consequence is that clinical trials only quantify EPA/DHA efficacy while concurrently failing to quantify efficacy of other active nutrients and freshness factor, which studies are beginning to show are also important for fish oil potency.
To further complicate matters in Omega 3 research and clinical medicine, different Omega 3 molecules have different physiological actions, and for the two main Omega 3 molecules (EPA and DHA), the science community is divided on their use and/or importance. One group advocates using EPA alone since EPA may be stronger anti inflammation substance than DHA while other groups advocate that DHA is most important since it is the longest molecule and the most likely to be lacking in one's diet. DHA is especially known for its nerve cell building abilities and crucial for mental functioning. It would therefore be advantageous to have an agreed upon EPA/DHA ratio that would be suitable to a multitude of medical conditions.
Other problems often associated with fish oils are the off-putting odor and taste (e.g., a “fishy” smell and/or taste), which acts as a deterrent for supplementing ones diet with these oils/supplements. These off-putting odors and tastes are attributed to oxidation of the unsaturated fatty acids as Omega-3 fatty acids and other chemical components in fish oils (“oxidized fish oils”) during fish storage and the fish oil (i) rendering/purification, (ii) manufacture, and (iii) finished product storage processes. To make these oxidized fish oils more palatable, artificial flavoring(s) and taste masking agents are often added to further improve taste and increase the likelihood of consumption of these oxidized fish oils. In some instances, these oxidized fish oils are encapsulated within an encapsulating agent, including, for example, a thick gelatin coating/layer, which masks the fishy smells and tastes to increase ones desire to consume these oxidized fish oils. However, even though encapsulating fish oils may aid in masking the fishy smell, it should be further noted that fish oil oxidation continues to occur post-encapsulation—often increasing by more than 7.5 PoV and doubling in anisidine values (i.e., increased totox) within three weeks post-encapsulation. It should also be noted that these masking and encapsulating agents fail to completely obviate the “fishy” taste and smell, while also disadvantageously increasing production costs and manufacturing time for fish oil formulations.
Although masking agents and/or encapsulating agents are used as the current industry-wide solution to overcome the fishy smell and taste of these oxidized fish oils, a major underlying problem remains. Specifically, oxidized fish oils have decreased health benefits, decreased bioavailability, and increased toxicity attributed to (i) increased totox (i.e., totox >10) and (ii) decreased EPA and DHA concentrations (and ratios relative to each other) resulting from processing (i.e., extraction and purification) when compared to totox and EPA and DHA concentrations (and ratios relative to each other) in natural, endogenous fish oil in viable fish. It should be further noted that fish oil oxidation cannot be reversed. Thus, once fish oil becomes oxidized and/or rancid it remains oxidized thereby permanently having decreased health benefits and decreased bioavailability. Also, the products formed during the oxidation of oils (rancemates) are unsaturated aldehydes and ketones as well as other reactive unsaturated aliphatic hydrocarbons, known to be toxic.
In addition to the above mentioned problems, most, if not all, currently available fish oil(s)/fish oil supplements have been winterized (i.e., fractionated) thereby excluding some beneficial fatty acids initially present in these oils. Specifically, winterization is known in the art as the removal of glycerides (fat) with a melting point >0° C. from fish oil, thus potentially enhancing storability of these oils in low temperature environments. Winterization may occur by cooling the “neat fish oil” to approximately 0° C. thereby forming a liquid (oil)/crystal mixture and then separating the liquid portion (“olein”) from the solid/crystalline portion (“stearin”). As the stearin portion contains many valuable chemical components including various fatty acids that act synergistically with the olein portion, winterized oils may have decreased bioavailability and decreased health benefits due to the removal of the stearin portion. In addition to decreased bioavailability of winterized fish oil, winterization of fish oils adds increased complexity, increased cost, and increased time period(s) for manufacture/production of fish oil formulations.
Another major problem plaguing currently marketed fish oils (i.e., both over the counter and prescription fish oil formulations) is the lack of standardization in these formulations. In other words, fish oil formulations vary greatly in, for example, fatty acid content (e.g., Omega-3 fatty acid content, as well as Omega-6, 7, 9, 11, and 13 fatty acid content), EPA and DHA concentrations (and ratios relative to each other), and totox thereby resulting in vastly different physiological and medical benefits obtained from these formulations. For example, many currently marketed formulations only include (i) concentrated EPA, (ii) concentrated DHA, and/or (iii) concentrated mixtures of EPA and DHA, but these formulations lack (or are highly deficient) in other important Omega-3 fatty acids such alpha-Linolenic acid (ALA), eicosadienoic acid (EDA), and docosapentaenoic acid (DPA), as well as Omega-6, 7, 9, 11 and 13 fatty acids that are typically found in natural fish oils but are removed when producing these concentrated EPA and/or DHA formulations. Unlike natural fish oils which have a neutral charge, these concentrated EPA formulations, concentrated DHA formulations, and/or concentrated mixtures of EPA and DHA have high in ethyl ester content resulting in increased polarity and thereby lowering the viscosity of the oil which may affect its physiological functioning. As another example, (i) Omega-3 content and (ii) EPA and DHA concentrations and ratios greatly vary in non-concentrated “natural” fish oils depending on the fish oil source (i.e., the type of fish used to produce the oil), time of the year the fish were obtained, the location from which the fish were obtained, and the refinement methods used to render/purify the fish oil. These factors also result in highly variable physiological and medical benefits. Furthermore, reduced viscosities of concentrated and/or winterized fish oils will also reduce its ability to be included in function foods or topical formulations like skin cream as the oil will more easily separate from solids and will also make added micro-encapsulated drugs included in fish oil medicinal formulations more noticeable and less palatable.
Another set of problems is connected to non-standardization of vitamin co factors in fish oil, e.g. Vitamin A and D3. While the original and highly potent cod liver oil contains significant amounts of Vitamin A (up to 1000 IU/g) and D3 (up to 100 IU/g) most fish oils on the market today have low levels of these nutrients because they are lost during the purification process and refining of the oil. Since many researchers believe that Vitamin A and D3 are important co factors for proper Omega 3 function, some set/standardized values would be desirable.
Another important nutrient/hormone relevant to Omega 3 oil is the content of melatonin. This indole hormone is present in significant amounts in raw cod liver oil or tuna oil, but will typically be diminished during winterization and refining or in oil from fish in aqua culture where light is used to delay sex maturation (the light makes melatonin content in fish diminish). Since studies show that melatonin and Omega 3 exercise synergistic actions on a multiple of cell metabolic functions, it would be desirable to restore and/or supplement this amount but in many countries health authorities forbid adding melatonin to food.
As evidenced above, vast differences exist between the currently marketed fish oils, thus leading to vastly different physiological and medical benefits observed by users of these formulations. Thus, for at least the reasons, the above mentioned non-standardized fish oils, oxidized fish oils, winterized fish oils, and/or oxidized, winterized fish oils present multi-faceted problem(s) of decreased bioavailability, decreased health benefits, and/or highly unpredictable health benefits coupled with increased toxicity.